Method and apparatus for an ion filter of a mass spectrometer

ABSTRACT

An ion filter for a mass spectrometer, the apparatus compr sing an ion inodifier; an ion selector configured to select a subset of a sample of ions based on their mobility in a gas; and a controller configured to operate the ion modifier in a first mode to modify the ions selected by the ion selector to provide daughter ions, and configured to operate the ion modifier in a second mode to Coutput the ions selected by the ion selector;wherein the ion filter is adapted for providing output ions from the ion modifier to an in-take of a mass spectrometer.

FIELD OF INVENTION

The present invention relates to methods and apparatus for identifyingsubstances of interest, and more particularly to methods and apparatusfor selecting and/or modifying ions to assist in the identification of asubstance of interest in a sample. These methods and apparatus may beuseful in mass spectrometry and may employ ion mobility techniques.

BACKGROUND

There is a need to detect traces of substances of interest such asexplosives, narcotics and chemical warfare agents. Reliable and accurateidentification is critical. Analysis may be performed usingspectrometers, such as ion mobility spectrometers and/or massspectrometers.

Mass spectrometry works by ionizing chemical compounds to generatecharged molecules or molecule fragments and measuring theirmass-to-charge ratios. In a typical mass spectrometry procedure ions areseparated according to their mass-to-charge ratio, typically byaccelerating them and measuring the degree to which they are deflectedby an applied electric or magnetic field. Some mass spectrometersoperate using ion traps. Mass spectra reflect the relative abundance ofdetected ions as a function of their mass-to-charge ratio. The ions canbe identified by comparing known masses to the identified masses or bycomparing obtained spectra to known spectra. Ions of the samemass-to-charge ratio will undergo the same amount of deflection, but asingle mass-charge ratio may be associated with a number of differentspecies of ions.

Ion mobility spectrometers (IMS) can identify material from a sample ofinterest by ionizing the material (e.g., molecules, atoms) and measuringthe time it takes the resulting ions to travel a known distance under aknown electric field. This is known as time of flight ion mobilityspectrometry—TOFIMS. Each ion's time of flight can be measured by adetector, and the time of flight is associated with the ion's mobility.An ion's mobility relates to its mass and geometry. Therefore, bymeasuring the time of flight of an ion in the detector it is possible toinfer an identity for the ion. These times of flight may be displayedgraphically or numerically as a plasmagram. Other kinds of ion mobilityspectrometry also exist. For example, in differential ion mobilityspectrometry ions are selected based on the dependency of the ionmobility on electric field strength. To do this, ions may be subjectedto varying electric field strengths selected so that only ions having aselected differential mobility are able to pass though the spectrometer.For example, in field asymmetric ion mobility spectrometry ions areseparated by the application of a high-voltage asymmetric waveform atradio frequency (RF) combined with a DC voltage. As the electric fieldvaries, depending on the ratio of the high-field and low-field mobilityof an ion, it will migrate toward one or the other electrode. Only ionswith specific differential mobility will pass through the device.

Other ion mobility techniques use a flow of carrier gas which carry ionsbetween electrodes. Ions can be deflected from their path in the flow ofgas by an electric field applied between the electrodes across thedirection of (transverse to) the flow of carrier gas. By scanning thestrength of the applied field ions having different mobility can beselected.

SUMMARY OF INVENTION

Aspects and examples of the invention are set out in the appendedclaims.

BRIEF DESCRIPTION OF DRAWINGS

Embodiments of the disclosure will now be described by way of exampleonly with reference to the accompanying drawings in which:

FIG. 1 shows a very schematic diagram of three possible implementationsof the disclosure;

FIG. 2 shows a schematic part cut-away view of an ion filter;

FIG. 3 shows a schematic part cut-away view of another ion filter;

FIG. 4 shows a schematic part cut-away view of another ion filter; and

FIG. 5 shows a schematic part cut-away view of another ion filter.

In the drawings like reference numerals are used to indicate likeelements,

SPECIFIC DESCRIPTION

Embodiments of the disclosure provide an ion filter for a massspectrometer. As illustrated in the drawings, and explained in moredetail below, an ion filter may comprise an ion selector and an ionmodifier. The ion selector selects a subset of a sample of ions based ontheir mobility in a gas, The ion modifier may be controlled to eithermodify ions to provide daughter ions which in turn are provided to amass spectrometer for analysis, or to allow the subset of ions to passunmodified to the mass spectrometer.

The ion modifier may be arranged to modify only the subset of ionsselected by the ion selector, or it may be arranged to modify the sampleof ions before the ion selector selects a subset of the daughter ions,for example the ion modifier may be integrated in the ion selector orarranged between a source of samples of ions and the ion selector,

Selecting based on ion mobility may comprise selecting based ondifferential ion mobility, and/or based on the time of flight ionmobility, for example based on ion mobility at a selected electricfield, for example based on the ‘low field’ ion mobility in which theion mobility is not dependent on field strength (e.g. fields of up toabout 500 Vcm⁻¹) and/or based on any other mobility characteristic.

Embodiments of the disclosure enable a sample to be analysed to identifya substance of interest by operating the ion selector to select a firstsubset of ions from a sample, and allowing the first subset of ions topass unmodified for analysis in a mass spectrometer, and then operatingthe ion selector to select a second subset of ions from the same sample,and then operating the ion modifier to modify this second subset of ionsto output the daughter ions for analysis in the mass spectrometer. Thefirst subset of ions and the second subset of ions may be obtained fromthe same sample (e.g. from a single sample of vapour). However in someembodiments they may also be obtained from separate samples obtainedfrom the same substance of interest (e.g. from volatilising a singleswab of a substance of interest).

FIG. 1 illustrates three possible configurations of an ion filter for amass spectrometer. In the first illustration, FIG. 1-A shows an ionselector 4 arranged to obtain ions from an ion source 2, and to select asubset of these ions based on their mobility in a gas, The ion selector4 can then provide this subset of ions to an ion modifier 6 which may beoperated selectively to either (a) modify the subset of ions before theyare analysed by the mass spectrometer or (b) to allow the ions to passwithout modification. In the second illustration FIG. 1-B shows an ionmodifier 6 arranged to obtain ions from an ion source 2 and which may beoperated to modify the ions before providing them to an ion selector 4which may select a subset of these ions before they are provided to themass spectrometer to be analysed. In the third illustration the ionselector includes an integrated ion modifier 6, in this configurationthe ion selection apparatus itself includes an ion modifier 6. This ionmodifier 6 can be operated to modify at least some of the ions in theion selector 4, and the ion selector 4 can be operated to provide asubset of the ions from the ion source 2 (perhaps some of which may havebeen modified) for analysis in the mass spectrometer.

FIG. 2 shows an ion filter for a mass spectrometer, the apparatusillustrated in FIG. 2 is one example of the configuration illustrated inFIG. 1-A. The apparatus illustrated in FIG. 2 comprises an ion source 2arranged to provide ions to the ion filter. The ion filter comprises anion selector 4 and an ion modifier 6 arranged to provide selected and/ormodified ions to a mass spectrometer for analysis.

The ion source 2 may comprise an inlet 20, such as a pinhole or membraneinlet, for obtaining a sample of gaseous fluid such as a vapour or gas,and an ioniser 18 for ionising the sample. The ioniser 18 may comprise asource of ionising radiation such as a corona discharge element or aradioactive source. In some embodiments the sample may be ionised usingan ionised reactant gas.

The ion selector 4 shown in FIG. 2 comprises a drift chamber separatedfrom the ion source 2 by a first ion gate 14. The ion selector 4 maycomprise a second ion gate 16, separated from the first ion gate 14 bythe drift chamber. The first ion gate 14 and the second ion gate 16 mayeach comprise two electrodes which may each comprise a plurality ofelongate conductors. The electrodes of each ion gate may beinterdigitated or, in another configuration, interleaved and at leastpartially non-coplanar (e.g. spaced apart in a direction of travel ofthe ions), for example to provide an ion shutter such as aBradbury-Nielsen gate, or a Tyndall-Powell gate.

The drift chamber may comprise a series of drift electrodes 26, 28 forapplying a voltage profile along the drift chamber to move ions from thefirst ion gate 14 along the drift chamber toward the second ion gate 16.The ion modifier 6 may be arranged for ions to pass from the driftchamber, through the second ion gate 16 into the ion modifier 6 beforebeing passed on to a mass spectrometer (not shown in FIG. 2).

The ion modifier 6 may comprise two electrodes which may be spaced apartfrom the second ion gate 16. Each of the ion modifier electrodes cancomprise an array of conductors, such as a grid, for example a mesh,arranged across the direction of travel of the ions from the second iongate 16 towards an outlet which may be coupled for providing ions to amass spectrometer. As illustrated, the conductors of each ion modifierelectrode may have gaps between them such that ions can pass througheach electrode by travelling through the gaps. In one example ions passthrough the gaps between the conductors of the electrode into a regionbetween the electrodes and subsequently out of the region through thegaps between the conductors of the ion modifier 6. While the ions are inthe region between the electrodes they can be subjected to a radiofrequency, RF, electric field to fragment them. For example the ionmodifier may be configured to subject ions to an alternating electricfield which is symmetric (e.g. has a small or zero DC component). Insome embodiments the ion modifier 6 may comprise a heater in addition toor as an alternative to these two electrodes. In some embodiments theion modifier 6 may comprise more than two electrodes. In some examplesof the disclosure more than one ion modifier may be used.

In the apparatus illustrated in FIG. 2, the ion selector comprises theion modifier 6, in that example it is arranged between the first iongate 14, and the second ion gate 16. In other examples in which the ionselector comprises the ion modifier 6 one or more ion gates of the ionselector (such as the first ion gate 14, and the second ion gate 16illustrated in FIG. 2) may be provided by an ion modifier 6, for exampleby a combined ion gate and ion modifier as described below. Examples ofa combined ion gate and ion modifier are provided in the applicant'sco-pending European patent application published as EP2666183, theentirety of which is hereby incorporated by reference.

A voltage provider 22 may be coupled to the ioniser 18, the first iongate 14, the second ion gate 16, the drift electrodes 26, 28, and theion modifier 6. A controller 24 may be coupled to control operation ofthe voltage provider 22.

A drift gas circulation system 8 may be coupled to a drift gas outlet 10of the ion selector 4, and to a drift gas inlet 12 of the ion modifier6. The ion modifier 6 may be arranged so that drift gas introduced inthe ion modifier 6 flows through the second ion gate 16 into the driftchamber towards the first ion gate 14. The drift gas circulation system8 may be configured to provide a flow of drift gas in a directiongenerally opposite an ion's path of travel from the first ion gate 14 tothe second ion gate 16. Example drift gases include, but are not limitedto, nitrogen, helium, air, air that is re-circulated (e.g., air that iscleaned and/or dried). It will be appreciated in the context of thepresent disclosure that in the example illustrated in FIG. 2, anelectric field is applied by the voltage provider (e.g. using the driftelectrodes and possibly also other electrodes) to move ions against thisflow of drift gas along the drift chamber towards the second ion gate16.

The first ion gate 14 may be operable to be opened to allow ions to passfrom the ion source 2 into the drift chamber, and operable to be closedto inhibit the passage of ions. Likewise, the second ion gate 16 may beoperable to be opened to allow ions to pass from the drift chamber tothe ion modifier, or to be closed to inhibit the passage of ions. Thisprovides one way to select a subset of ions from a sample. Selecting asubset of ions (e.g. less than all of the ions from the sample) maycomprise allowing some ions from a sample to pass the first ion gate 14,and then inhibiting the passage of some of these ions through the secondion gate 16, for example by closing the second ion gate 16. Accordingly,the controller 24 may select a subset of a sample of ions based on theirmobility in the drift gas by controlling the relative timing of openingthe first ion gate 14 and the second ion gate 16. For example the timingof opening the second ion gate 16 may be selected based on the timing ofopening the first ion gate 14 to allow only those ions having a selectedtime of flight along the drift chamber (and/or a selected range orranges of times of flight) to pass from the ion selector 4 to the ionmodifier.

The ion modifier 6 may be operable in a first mode to apply energy toions to modify them, for example by raising their effective temperature,for example by subjecting the ions to an RF electric field. The energyapplied to the ions in this first mode of operation may be selectedbased on the amount of energy required to fragment selected ions, forexample ions of a target substance, and adduct ions formed between thattarget substance and a known reactant that is present in the ion source2 or the ion selector 4. Target substances include narcotics,explosives, chemical warfare agents and other contraband. The energyapplied may be selected by controlling the amplitude and/or frequency ofthe electric field applied by the ion modifier. In some embodiments theenergy may be thermal energy and the amount of energy applied may becontrolled by controlling temperature, for example using a heater. Theion modifier may also be operable in a second mode to allow ions to passfrom the ion selector 4 to the mass spectrometer without subjecting theions to energy to modify them, For example, in this second mode the ionmodifier may be operated to apply less energy to the ions than isapplied in the first mode, for example it may be switched off.

In operation, the ioniser 18 is operated to provide a sample of ionsfrom a substance of interest. The controller 24 may then open the firstion gate 14 to allow some ions from the sample to travel along the driftchamber against the flow of drift gas. The time of arrival of the ionsat the second ion gate 16 is determined by their mobility through thegas and the electric field applied along the drift chamber by the driftelectrodes 26, 28. The controller 24 then controls the second ion gate16 to inhibit the passage of some of the ions and to allow others topass. For example, ions which arrive at the second ion gate 16 in aselected time window (or a series of time windows) after the opening ofthe first ion gate 14 may be allowed to pass through the second ion gate16 while ions arriving outside of this window (or windows) may beinhibited from passing for example by being stopped or deflected by theion gate. Accordingly, only a selected subset of ions from the ionsource 2 may be passed through the ion selector 4 to the ion modifier.

The controller 24 can then operate the ion modifier 6 in either (a) thefirst mode to modify this selected subset of ions and to provide thedaughter ions obtained by this modification process to the massspectrometer, or (b) the second mode to allow the selected subset ofions to pass through to the mass spectrometer without modifying them.For example, the controller 24 may first select a subset of ions from asample to be passed to the mass spectrometer, and operate the ionmodifier in the second mode to provide the (unmodified) subset of ionsto the mass spectrometer. The controller 24 may then subsequentlyprovide a second subset of ions to the ion modifier and operate the ionmodifier in the first mode so that daughter ions can be provided to themass spectrometer. The subset of ions provided without modification, andthe daughter ions obtained by modifying a subset of ions may be acomparable subset (e.g. a subset from the same sample and/or having thesame mobility/mobilities), Both subsets may then be analysed in the massspectrometer to identify the substance of interest.

The order of operation explained above may also be reversed so that thedaughter ions are provided to the mass spectrometer first, and theparent ions are provided subsequently. The first and second subset ofions may be from the same sample, and may be selected to have the samemobility/mobilities, e.g. by using the same time window(s) for openingand closing the ion gates.

In some embodiments, the controller 24 may control the timing ofoperation of the ion modifier 6 in the first mode so that only some(e.g. less than all) of the selected subset of ions are modified, Forexample where the selected subset of ions passes through the ionmodifier during a particular time window (or windows) e.g. as determinedby their mobility, the controller 24 may operate the ion modifier tomodify ions during a selected interval during this time window.

As mentioned briefly above, in some embodiments the first ion gate 14 orthe second ion gate 16 may be provided by one or more electrodes of theion modifier 6. For example, the controller 24 may be configured toapply a voltage to the ion modifier 6 to inhibit the passage of ionsthrough the ion modifier and/or to deflect ions travelling along thedrift chamber so that the ion modifier performs the function of thesecond ion gate. For example, the controller may be configured tooperate a first electrode of the ion modifier 6 as an ion gate. Forexample, one electrode of the ion modifier 6 may comprise a plurality ofconductors arranged to be operated as an ion gate, for example an ionshutter such as a Bradbury-Nielsen gate, or a Tyndall-Powell gate. Anyof the ion gates of any of the embodiments described herein may beprovided by an ion modifier arranged in this way. Examples of combinedion gates and ion modifiers are provided in the applicant's co-pendingEuropean patent application published as EP2666183, the entirety ofwhich is hereby incorporated by reference. In some embodiments theapparatus comprises more than one ion modifier 6.

In some examples the apparatus of FIG. 2 only comprises a single iongate, and that ion gate may be provided by a combined ion gate and ionmodifier, for example provided by one or more electrodes of the ionmodifier 6.

In the example illustrated in FIG. 2, the drift gas circulation system 8is arranged to provide a flow of drift gas through both the ion selector4 and the ion modifier 6, for example, in the configuration shown inFIG. 2 the ion selector 4 and ion modifier 6 may be at the same gaspressure. In some examples however, ions may be passed from the ionselector 4 (e.g. from the second ion gate 16) to the ion modifierthrough a narrow passage arranged to permit a gas pressure difference tobe maintained between the two.

FIG. 3 illustrates a configuration similar to that shown in FIG. 2, butin the example shown in FIG. 3 the ion modifier and the ion selector maybe arranged in separate chambers, By pumping on one or both of the twochambers the pressure in each chamber may be controlled separately, forexample a pressure difference may be maintained between them. Asillustrated, in these embodiments, the use of a narrow passage, such asa capillary 30, allows ions to travel between the ion selector and theion modifier 6. Ion focussing apparatus such as an ion guide may bearranged to direct ions along this narrow passage. In this configurationthe pressure in the ion selector and/or the ion modifier 6 may be atleast 500 millibar, for example at least 800 millibar, for example aboutatmospheric pressure, The gas pressure in the ion modifier 6 may bedifferent from, e.g. lower than, the pressure in the ion selector.

It will be appreciated that the configuration shown in FIG. 3 may bereversed so that the ion modifier 6 is arranged between the ion source 2and the ion selector, for example the ion source 2 may be arranged toprovide ions to the ion modifier 6, and the controller 24 can selectwhether or not to operate the ion modifier 6 to modify these ions beforethey are passed to the ion selector. In this configuration the ionmodifier 6 and the ion source 2 may be arranged in separate chambers(which may be at different pressures), and as described with referenceto FIG. 3 ions may be passed from the ion modifier 6 to the ion selectoralong a narrow passage such as a capillary 30. In this configuration theion selector may be operated to select a subset of daughter ionsproduced by the ion modifier 6, and the ion modifier 6 can be operatedin either the first mode to modify ions or in the second mode to allowunmodified ions to pass to the ion selector.

FIG. 4 illustrates another example similar to that shown in FIG. 2. InFIG. 4, as in FIGS. 2 and 3 the ion selector is based on a time offlight ion mobility spectrometry method—for example wherein thecontroller 24 is configured to select the subset of ions by controllingthe timing of operating the second ion gate 16. In the apparatusillustrated in FIG. 4, the second ion gate 16 is arranged between theion modifier 6 and the output to the mass spectrometer, for example theion modifier 6 may be arranged in the drift chamber between the firstion gate 14 and the second ion gate 16 of the ion selector. Asillustrated in FIG. 4, the ion modifier 6 may be arranged to modify ionsin a region in the drift chamber of the ion selector, for example theion modifier 6 may comprise two electrodes as described above withreference to FIG. 2, and these may be arranged to subject ions in thisregion to electric fields (ag. RF electric fields) which are strongerthan the electric fields used to move ions along the drift chamber. Theion modifier 6 electrodes may be arranged to subject the ions to anelectric field aligned with the direction of travel of the ions alongthe drift chamber. The alignment of the electric field from the ionmodifier 6 with the direction of travel of the ions is unlikely to beperfect or uniform. For example the direction of the electric field willdepend on the geometry and relative arrangement of the conductors whichmake up the ion modifier electrodes.

FIG. 5 illustrates an ion filter for a mass spectrometer in which an ionselector is configured to select a subset of ions based on adifferential mobility technique such as a differential mobilityanalysis.

The apparatus of FIG. 5 may comprise an ion source 2 having the featuresof the ion source 2 described above with reference to FIG. 2.

The ion selector shown in FIG. 5 comprises a gas flow chamber separatedfrom the ion source 2 by a first ion gate 14. The gas flow chamber maybe arranged to allow ions to be carried by a flow of gas from the ionsource 2 towards an outlet of the gas flow chamber. A carrier gas flowsystem may be arranged to provide the flow of carrier gas along the gasflow chamber from the ion gate 14 to the outlet. Two deflectingelectrodes are arranged for applying an electric field in the gas flowchamber across the direction of (e.g, transverse to) the flow of gas.

A voltage provider 22 may be coupled to the ioniser 18, the ion gate 14,and the ion modifier electrodes also as described above with referenceto FIG. 2. The voltage provider 22 may also be coupled to the deflectionelectrodes for applying a selected electric field perpendicular to thedirection of the flow of gas.

A controller 24 is coupled to control the voltage provider 22 foroperating at least one of the ioniser 18, the ion gate 14, thedeflection electrodes, and the ion modifier 6. The controller 24 may beconfigured to control the electric field applied by the deflectionelectrodes so that only ions having a selected mobility characteristic,for example a selected differential mobility, are able to pass from theion selector to be provided to the mass spectrometer for analysis.

As illustrated in FIG. 5, the outlet of the ion selector is arranged sothat ions which leave the ion selector can be passed to the ion modifier6. The ion modifier 6 may comprise two electrodes and have the featuresdescribed above with reference to the ion modifier 6 illustrated in FIG.2, the ion modifier 6 of this embodiment may also be arranged in aseparate chamber as described above with reference to FIG. 3, orarranged to modify ions before (or during) their separation by the ionselector as described above with reference to FIG. 4. In operation, ionsare provided from the ion source 2 into the flow of carrier gas. Theflow of gas carries the ions towards the outlet of the ion selector. Thevoltage provider 22 applies a voltage across the deflection electrodes,to provide an electric field transverse to (e.g. perpendicular to) thedirection of the flow of gas. The controller 24 selects the appliedvoltage to control this electric field, and this in turn selects themobility of ions which are able to pass through the outlet of the ionselector. The controller 24 can then operate the ion modifier 6 in oneof the first mode and second mode described above to modify the selectedsubset of ions, or to allow them to pass unmodified to the massspectrometer. In the embodiment of FIG. 5, the ion gate 14 is optional.

The methods of operation described above with reference to FIGS. 1 to 4may also be applied to the apparatus described with reference to FIG. 5.

It will be understood that the embodiments described are to beunderstood as illustrative examples. Further embodiments are envisaged.For example a field asymmetric ion mobility spectrometry technique maybe used to provide the ion selector. These embodiments may reflect theconfiguration illustrated in FIG. 5 and the voltage provider 22 may beconfigured to apply an asymmetric alternating voltage, for example an RFvoltage, as will be appreciated by the skilled addressee in the contextof the present disclosure this may enable a subset of ions to beselected based on the electric field dependence of their mobility, forexample based on their differential mobility. In some embodiments of theapparatus illustrated in FIG. 5 in addition to, or as an alternative tothe use of a carrier gas a voltage may be used to move ions towards theoutlet, for example electrodes similar to the drift electrodes 26, 28illustrated in FIG. 2 may be used.

It will also be appreciated that any of the apparatus embodimentsdescribed herein may be used in methods of identifying a substance ofinterest. For example they may be coupled to mass spectrometers toenable mass spectrometry data (and perhaps also mobility data)associated with both modified and unmodified ions to be used inidentifying the substance of interest—for example to assign one or morecandidate identities to the substance. One example of such a methodcomprises ionising a sample of a substance.

A subset of these ions can then be selected, for example using any oneof the ion selectors described herein. This first subset of sample ionsmay be selected to have a particular mobility characteristic, such as aparticular ion mobility, for example a particular differential mobility.This first subset of sample ions may then be provided to a massspectrometer to obtain first mass spectrometry data, for exampledescribing the mass to charge ratios of that subset of ions.

A second subset of ions from the sample may then be obtained (forexample by selecting them based on the same mobility characteristic, forexample to have the same mobility characteristic(s) as the first subsetof ions) of the sample ions.

This second subset of ions may then be modified, for example byfragmenting the ions for example by subjecting them to an alternatingelectric field. The daughter ions produced by this modification processcan then also be provided to the mass spectrometer to obtain second massspectrometry data.

The first mass spectrometry data and the second mass spectrometry datamay then be used in identifying the substance of interest. It will ofcourse be appreciated that the order in which these steps are performedmay be reversed. In addition, the mobility characteristic of at leastone of the first subset of ions and the second subset of ions may alsobe used in identifying the substance of interest. Identifying thesubstance of interest may comprise assigning one or more candidateidentities to the substance.

It is to be understood that any feature described in relation to any oneembodiment may be used alone, or in combination with other featuresdescribed, and may also be used in combination with one or more featuresof any other of the embodiments, or any combination of any other of theembodiments. Furthermore, equivalents and modifications not describedabove may also be employed without departing from the scope of theinvention, which is defined in the accompanying claims.

For example, the following methods of the disclosure may also becombined with any other method described herein, and/or implementedusing any of the apparatus described herein. A first such examplecomprises introducing a sample of vapour into a low pressure region of aspectrometry apparatus, ionising the sample, modifying the ions obtainedby ionising the sample, and providing the modified ions to a detectorfor analysis. The gas pressure in the low pressure region may be lowerthan ambient pressure by at least 200 mb, for example lower than ambientpressure by at least 300mb. Such methods may comprise moving the ionsaway from an ionisation region towards the detector and subjecting theions to a radio frequency, RF, electric field having a component (forexample a dominant component) aligned with the direction of movement ofthe ions towards the detector. The RF electric field may be applied tothe ions by two electrodes spaced apart in the direction of movement ofthe ions towards the detector.

Some examples of the disclosure may be used to provide sample intakestage apparatus for spectrometers such as mass spectrometers. Theseintake stages may comprise a low pressure region having a pressure lowerthan 200mb less than ambient pressure, the low pressure region maycomprise an inlet 20 for obtaining a sample of gaseous fluid, an ioniser18 for obtaining parent ions from the sample, and an ion modifier 6configured to modify the parent ions in the low pressure region toprovide daughter ions, and an outlet arranged for providing the daughterions to the spectrometer for analysis. The ion modifier 6 may bearranged to subject the ions to an alternating radio frequency, RF,electric field aligned with, for example predominantly aligned with, thedirection of movement of the ions towards the outlet.

With reference to the drawings in general, it will be appreciated thatschematic functional block diagrams are used to indicate functionalityof systems and apparatus described herein. It will be appreciatedhowever that the functionality need not be divided in this way, andshould not be taken to imply any particular structure of hardware otherthan that described and claimed below. The function of one or more ofthe elements shown in the drawings may be further subdivided, and/ordistributed throughout apparatus of the disclosure. In some embodimentsthe function of one or more elements shown in the drawings may beintegrated into a single functional unit. Some types of ion mobilityspectrometry have been described for providing the ion selectorfunctions of the apparatus described herein but it will be appreciatedthat any ion mobility based technique may be used, for example other ionmobility techniques such as travelling wave IMS techniques. Otherexamples and variations will be apparent to the skilled addressee in thecontext of the present disclosure.

For example, drift gases need not be used, some examples of thedisclosure may be used in systems where the mean free path of ions iscomparable to, for example greater than or equal to, the length of thedrift chamber. Rather than mobility, these examples of the disclosuremay measure the mass to charge ratio of the ions for example based on atime of flight measurement or based on subjecting ions to a magneticfield to deflect them from their direction of travel.

In some examples, one or more memory elements can store data and/orprogram instructions used to implement the operations described herein.Embodiments of the disclosure provide tangible, non-transitory storagemedia comprising program instructions operable to program a processor toperform any one or more of the methods described and/or claimed hereinand/or to provide data processing apparatus as described and/or claimedherein.

The uses and operations of the apparatus described herein are intendedalso as a disclosure of the method, and the particular structure of theapparatus may not be relevant—therefore features of apparatusembodiments may be combined with the method embodiments described andclaimed herein. Likewise, the methods described herein may beimplemented by suitable configuration of the apparatus disclosed herein.Where appropriate, the activities and apparatus outlined herein may beimplemented using controllers and/or processors which may be provided byfixed logic such as assemblies of logic gates or programmable logic suchas software and/or computer program instructions executed by aprocessor. Other kinds of programmable logic include programmableprocessors, programmable digital logic (e.g., a field programmable gatearray (FPGA), an erasable programmable read only memory (EPROM), anelectrically erasable programmable read only memory (EEPROM)), anapplication specific integrated circuit, ASIC, or any other kind ofdigital logic, software, code, electronic instructions, flash memory,optical disks, CD-ROMs, DVD ROMs, magnetic or optical cards, other typesof machine-readable mediums suitable for storing electronicinstructions, or any suitable combination thereof.

Where reference is made to electrodes it will be appreciated that anyarrangement of conductors may be used, for example electrodes maycomprise metals or other conductors and may be at least partiallyexposed and/or partially insulated, The voltage providers describedherein may comprise an AC power supply, which may comprise one or morestep-up or step down transformers, the voltage providers may alsocomprise DC power supplies such as batteries or fuel cells or capacitivepower stores. Combinations of AC and DC power may be used and thevoltage provider may comprise an inverter for providing an AC voltagebased on a DC power supply. In some embodiments the voltage provider maycomprise rectifiers for providing DC voltage based on an AC powersupply. Any combination of AC and DC power supply and voltage providingcomponents may be used. In some embodiments the voltage provider mayalso operate as a current source.

1. An ion filter apparatus for a mass spectrometer, the apparatuscomprising: an ion modifier comprising two electrodes, the electrodescomprising conductors arranged across the direction of travel of ions;an ion selector comprising a first ion gate and a second ion gate,configured to select a subset of a sample of ions based on theirmobility in a gas; and a controller configured to operate the ionmodifier in a first mode to modify the ions selected by the ion selectorto provide daughter ions, and configured to operate the ion modifier ina second mode to output the ions selected by the ion selector; whereinthe ion filter includes an outlet, the outlet adapted for providingoutput ions from the ion modifier to an intake of a mass spectrometer,wherein the ion selector is separated from the outlet by the ionmodifier.
 2. An ion filter apparatus for a mass spectrometer, theapparatus comprising: an ion selector comprising a first ion gate and asecond ion gate; an ion modifier comprising two electrodes, theelectrodes comprising conductors arranged across the direction of travelof ions, the ion modifier arranged to receive a sample of ions; and acontroller configured to operate the ion modifier in a first mode tomodify the sample of ions to provide daughter ions, and configured tooperate the ion modifier in a second mode to output the sample of ions;wherein the ion selector is configured to select a subset of ions fromthe ion modifier based on their mobility in the gas, and the ion filterincludes an outlet, the outlet adapted for providing the selected subsetof ions to an intake of a mass spectrometer, wherein the ion modifier isseparated from the outlet by the ion selector.
 3. The apparatus of claim2 wherein the ion selector comprises the ion modifier.
 4. An ion filterapparatus for a mass spectrometer, the apparatus comprising: an ionmodifier comprising two electrodes, the electrodes comprising conductorsarranged across the direction of travel of ions; an ion selectorcomprising a first ion gate and a second ion gate, the second ion gateseparated from the first ion gate by a drift chamber and the ionmodifier, the ion selector configured to select ions based on mobilityof the ions in a gas, and a controller configured to operate the ionmodifier to modify parent ions to provide daughter ions having adifferent mobility in the gas from the parent ions, wherein the ionselector is configured to select, based on their mobility in the gas, asubset of ions obtained from the ion modifier and the ion filterincludes an outlet, the outlet adapted to provide the selected subset ofions to the mass spectrometer.
 5. The apparatus of claim 4 wherein thecontroller is configured to select whether to: (a) operate the ionmodifier in a first mode to modify ions to output daughter ions; or (b)to operate the ion modifier in a second mode to output unmodified parentions.
 6. The apparatus of claim 1 wherein the controller is configuredto: operate the ion selector to select a first subset of ions from asample, operate the ion modifier in the second mode to output the firstsubset of ions; operate the ion selector to select a second subset ofions from the sample, and operate the ion modifier in the first mode tooutput daughter ions.
 7. The apparatus of claim 6 wherein the ionselector is configured to select the first subset of ions and the secondsubset of ions so that, prior to operation of the ion modifier, thefirst subset of ions and the second subset of ions have the samemobility.
 8. The apparatus of claim 2 wherein selecting ions based onmobility in a gas comprises selecting ions based on one of differentialion mobility and ion mobility.
 9. The apparatus of claim 2 wherein theion modifier is arranged to modify ions in a region having a gaspressure of at least 500 millibar.
 10. The apparatus of claim 2 whereinthe ion selector is arranged to select ions based on their mobility in agas having a gas pressure of at least 500 millibar.
 11. The apparatus ofclaim 2 wherein the ion selector comprises a first electric fieldapplier configured to move ions through a drift gas towards an ion gate,the first electric field applier comprising at least one firstfield-applier electrode.
 12. The apparatus of claim 11 wherein thecontroller is configured to select the subset of ions by controlling thetiming of operating the ion gate.
 13. The apparatus of claim 11 whereinthe ion modifier comprises a second electric field applier configured tosubject ions to an alternating electric field aligned with a directionof travel of the ions through the ion modifier, the second electricfield applier comprising at least one second field-applier electrode.14. The apparatus of claim 2 wherein the ion selector is arranged toapply a deflecting electric field to deflect ions carried in a flow ofgas, and the controller is configured to control the deflecting field toselect the subset of ions.
 15. The apparatus of claim 14 wherein the ionselector comprises one of a scannable ion filter, a differential ionmobility spectrometer and a field asymmetric ion mobility spectrometer.16. The apparatus of claim 2 wherein the ion modifier is adapted toapply an alternating electric field having a frequency of at least 2.5MHz to fragment ions. 17.-28. (canceled)
 29. The apparatus of claim 4wherein the ion modifier is arranged to modify ions in a region having agas pressure of at least 500 millibar.
 30. The apparatus of claim 4wherein the ion selector is arranged to select ions based on theirmobility in a gas having a gas pressure of at least 500 millibar.